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Biomedical subjects

M Sawada

Publications and source records attributed to M Sawada.

At least 289 records · Page 16Linked to original sources

Recombinant human IL-5 augments immunoglobulin generation by human B lymphocytes in the presence of IL-2.

The biological activity of interleukin-5 (IL-5) on human B lymphocytes was examined by using a newly purified recombinant human IL-5 preparation. Different densities of B cells from human tonsil samples were isolated by Percoll density gradient from nonrosetted cells. The IL-5 preparation did not act as a B cell growth factor on the large (in vivo-activated) or small (resting) B cells after activation with polyclonal B cell activators. The IL-5 augmented the immunoglobulin (Ig) generation of Staphylococcus aureus Cowan strain I (SAC)-activated B blasts in the presence of interleukin-2 (IL-2). The effect of IL-5 on Ig generation was greater in pokeweed mitogen (PWM)-driven B blasts than that in SAC-induced B blasts when assessed by enzyme-linked immunosorbent assay. The amounts of mu RNA isolated from IL-5/PWM-treated cells were also larger than those from IL-5/IL-2-treated B blasts. These results suggest that the human IL-5 can increase Ig generation of B cells in the presence of IL-2 by working at the level of mRNA coding for Ig.

B-Lymphocytes↗

Brain vessels near muscle autografts are sites for entry of isogeneic macrophages into brain.

An autograft of skeletal muscle on rat dorsal medulla is a permanent opening in the blood-brain barrier to solutes. Is the graft also a site for the entry of exogenous, isogeneic leukocytes? Five weeks after inserting the graft, peritoneal macrophages (M phi) from inbred Fischer rats were activated by phorbol myristate acetate, labeled with a fluorescent dye, and infused as a bolus of about 2 x 10(6) cells into the axillary artery of Fischer hosts. The cells circulated for 2 h. The brains were then fixed, frozen, and sectioned. Only when M phi had been activated and a muscle autograft inserted did appreciable numbers of M phi enter the medulla. Nonactivated M phi invaded the grafts but very few entered the brain at 2 h. In rats with gel foam grafts, only a few activated M phi invaded gel and brain. Before entering tissues, M phi must adhere to the lumenal face of vessels. Cell adhesion molecules, e.g., I-CAM-1 and its ligand adhesion molecule, leukocyte function antigen (LFA-1), are known to mediate adhesion. I-CAM-1, detected immunohistochemically, increased in graft vessels and in nearby brain vessels. The rise may have been mediated by cytokines, interleukin-6, and tumor necrosis factor-beta, found in the grafts. LFA-1, however, assayed by fluorescence-activated cell sorting, was on both activated and nonactivated, exogenous M phi. Thus, M phi-endothelial attachment may have involved other adhesion molecules, e.g., selectins. The autograft also induced major histocompatibility complex class I on microglia and classes I and II on brain vessels near the graft. These vessels, by expressing adhesion molecules, are entry routes into brain for activated, isogeneic leukocytes that can then migrate for a limited distance of 1-2 mm in an otherwise intact brain.

Animals↗

Adenocarcinoma in a benign cystic teratoma of the ovary: report of a case with a long survival period.

We report a case of adenocarcinoma associated with benign cystic teratoma (dermoid cyst) of the ovary in which the patient has survived for a long time. A 62-year-old woman underwent abdominal total hysterectomy with bilateral salpingo-oophorectomy on March 16, 1976 because of a large left ovarian tumor. There were no pathologic findings in other intra-abdominal organs. The tumor was cystic, contained dark and mucinous sebaceous material with hair, and weighed 15 kg. Papillary growths protruded into the cavity in some areas of the wall. Microscopically and immunohistochemically, the tumor was characterized as a mucinous adenocarcinoma associated with dermoid cyst, suggesting a possible gastrointestinal origin. After the surgery, she was treated with chemotherapy and is alive and well more than 15 years later. Our review of the literature indicates that, while it is widely held that patients with adenocarcinoma associated with dermoid cyst do not survive, many in fact do survive for a long period after surgery.

Adenocarcinoma, Mucinous↗

Immunohistochemical study of proliferating cell nuclear antigen (PCNA) in endometrial carcinoma with argyrophil cells.

We performed an immunohistochemical study of argyrophil cells in 10 endometrial carcinomas using the monoclonal antibody PC 10 to detect proliferating cell nuclear antigen (PCNA). Formalin-fixed, paraffin-embedded sections of 10 endometrial carcinomas containing argyrophil cells which are chromogranin positive (four containing type I cells, two type II, and four mixed-type I and type II) were stained with monoclonal antibody PC 10. In addition, one of the tumors with mixed-type cells was transplanted into nude mice, and the tumors which developed in subpassages were also analyzed for PCNA. Argyrophil cells in 10 endometrial carcinomas were found to be negative immunohistochemically for PCNA, regardless of their type, suggesting that they are not proliferating. Surprisingly, however, all subpassaged tumors contained argyrophil cells which were also negative for PCNA. From these results, it may be postulated that argyrophil cells were induced through differentiation to neuroendocrine direction of neoplastic cells.

Adenocarcinoma↗

Immunohistochemical study of cytokeratin 7 for the differential diagnosis of adenocarcinomas in the ovary.

Mucinous adenocarcinomas of the ovary were studied immunohistochemically for cytokeratins 7 and 18, either to determine whether the ovarian tumor was primary or a metastasis or to establish the histogenetic origin of the tumor. Primary ovarian tumors were strongly positive for both cytokeratins, while ovarian metastases from colonic cancers were negative for cytokeratin 7, as were the colonic cancers. Three of four ovarian tumors complicated by pseudomyxoma peritonei were negative for cytokeratin 7, indicating appendiceal origin. Two of seven mucinous tumors associated with dermoid cysts were negative for cytokeratin 7, suggesting gastrointestinal origin.

Adenocarcinoma, Mucinous↗

Inositol 1,4,5-trisphosphate mediates adrenaline activation of K+ conductance in mouse peritoneal macrophages.

In mouse peritoneal macrophages, alpha 1-adrenoceptor stimulation evokes a Ca(2+)-dependent K+ current [Io(Adr)][Hara et al. (1991) Pflügers Arch 419:371-379]. The roles of D-myo-inositol 1,4,5-trisphosphate (InsP3) and a GTP-binding protein (G protein) in Io(Adr) were investigated with tight-seal whole-cell recordings and fura-2 fluorescence measurements. Intracellular injection of InsP3 (5-50 microM) evoked transient outward currents [Io(InsP3)] with or without damped oscillations in membrane currents at -40 mV. Dialysis with 0.2 mM guanosine 5'-[3-thio]triphosphate (GTP[gamma S], a poorly hydrolysable GTP analogue) at -40 mV activated oscillatory outward currents or a slowly developing steady current on which such oscillations were superimposed after a delay of 10-90 s. Io(InsP3) and the GTP[gamma S]-induced current [Io(GTP[gamma S])] were accompanied by an increase in conductance. Reversal potentials of both responses closely depended on the extracellular K+ concentration. Fura-2 measurements revealed that Io(InsP3) and Io(GTP[gamma S]) result from a rise in intracellular free Ca2+ concentration ([Ca2+]i). Removal of extracellular Ca2+ did not abolish Io(InsP3) and Io(GTP[gamma S]). Both were blocked by bath-applied charybdotoxin. Intracellular D-myo-inositol 1,3,4,5-tetrakisphosphate (InsP4, 50 microM) did not evoke any responses, whereas D-myo-inositol 2,4,5-trisphosphate [InsP3(2,4,5), 20 microM] elicited an outward current at -40 mV. Io(InsP3) was completely blocked by prior dialysis with the InsP3 receptor antagonist heparin (5 mg/ml). Inclusion of guanosine 5'-[2-thiol] diphosphate (GDP[beta S], 2 mM) or heparin (5 mg/ml) together with GTP[gamma S] in the patch pipette solution completely blocked Io(GTP[gamma S]). These results indicate that intracellular injection of InsP3 or GTP[gamma S] mimic Io(Adr).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Selective effects of human immunodeficiency virus (HIV) gp120 on invertebrate neurons.

1. HIV gp120 selectively reduces the glutamate-induced inward current and the acetylcholine-induced outward current in specific and identified Aplysia neurons without affecting dopamine (DA)- and serotonin (5-HT)-induced responses. 2. gp120 specifically decreases DA levels without significantly altering norepinephrine and 5-HT levels in Mytilus pedal ganglia. 3. The gp120-associated decrease in DA levels in Mytilus is dose dependent and exhibits a threshold level. 4. The alteration of in vitro DA levels is specific for gp120 since anti-gp120 blocks the effect. 5. gp120 and its effects appear to be stable due to the duration of treatment and the failure of secondary effects to materialize following antibody treatment.

Acetylcholine↗

The alpha 1A-adrenoceptor couples to Ca2+ mobilization in mouse peritoneal macrophages.

Activation of the alpha 1-adrenoceptor (alpha 1-AR) in mouse peritoneal macrophages induces a Ca(2+)-dependent K+ current via release of Ca2+ from internal stores [Hara et al. (1991) Pflügers Arch 419: 371-379]. In order to characterize the alpha 1-AR subtype in macrophages, we examined potencies of the alpha 1-AR subtype-selective antagonists against epinephrine-induced increases in intracellular Ca2+ concentration ([Ca2+]i). The Ki values for the alpha 1-AR in macrophages of WB4101, 5-methylurapidil and phentolamine were 0.13 nM, 0.15 nM and 7.0 nM, respectively. (+)-Niguldipine (10 nM) completely blocked the response. Treatment with chloroethylclonidine (CEC) did not abolish the response. These pharmacological properties of the alpha 1-AR in macrophages agree quite well with those of the alpha 1A subtype.

Animals↗

Changes in superoxide radical formation, lipid peroxidation, membrane fluidity and cathepsin B activity in aging and spawning male Chinook salmon (Oncorhynchus tschawytscha).

Superoxide radical (SOR) formation in the brain and the liver of male Chinook salmon (Oncorhynchus tschawytscha) increased in mitochondrial and plasma membrane samples as they aged. In 2-year-old salmon, spawning also lead to a significant elevation in SOR formation in mitochondrial and plasma membrane samples. The rise in this free radical was associated with an increase in lipid peroxidation, a decrease in plasma membrane fluidity, and an elevation in cathepsin B activity in the brain and liver. In 2-year-old spawning salmon, the changes in these parameters was greater than in 2-year-old non-spawning salmon. These observations suggest that free radical levels increase with aging and during spawning and indicate that these changes may be involved in cellular degeneration. In addition, these results support the suggestion that cellular degeneration accelerates during the spawning process.

Aging↗

Oxygen radicals and the control of ovarian corpus luteum function.

The superoxide radical (SOR) and other reactive oxygen species form in cells during the course of respiration as well as in response to various stimuli. Although well known for their damaging effects, these agents can also work beneficially to control cell function. The present review examines the evidence that oxygen radicals and H2O2 may regulate steroid hormone biosynthesis in the ovarian corpus luteum. Recent findings indicate that luteal cells can employ reactive oxygen species at specific sites in controlling the production of progesterone over the course of the reproductive cycle and in inhibiting its synthesis during regression at the end of the cycle. These studies indicate that oxygen radicals and related compounds may function as intracellular regulators of steroidogenesis in the corpus luteum.

Animals↗

Relationship between alcoholic liver disease and HCV infection.

The high prevalence of hepatitis C virus (HCV) markers in alcoholic liver cirrhosis (AL-LC) and hepatocellular carcinoma (HCC) suggests a close aetiopathogenic relationship between alcoholic liver disease (ALD) and HCV infection. In the present study, HCV markers in ALD were measured by the highly sensitive methods, and the changes of sequential HCV markers after abstinence in ALD patients were analysed in order to elucidate the effect of alcohol on HCV. Antibodies to HCV-related antigen were determined using the first or second generation test kit. HCV-RNA genomes encoding the NS-5 region were detected using the RT-PCR method. In the HCV-NS5 negative serum, HCV genomes of the 5'-noncoding region were detected using the two-stage PCR method. Titres of HCV-RNA were measured by multiple cyclic PCR and cDNA dot blotting. Typing of HCV genomes was carried out on the PCR product from the NS-5 region by slot blot hybridization using type-specific cDNA probes, or by restriction fragment length polymorphisms analysis. In alcoholic fibrosis and alcoholic hepatitis, the prevalence of HCV markers was low, suggesting that the main aetiological factor is alcohol but not HCV in these types of ALD. HCV markers were positive in the half of the patients with AL-LC, and in more than 80% of patients with AL-CH and AL-HCC, indicating that HCV infection closely relates to these types of ALD. The ratio of the K1 type to the K2 type of HCV genomes was 4:1 in all types of NANB liver disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Effects of alcohol on the replication of hepatitis C virus.

We have reported that hepatitis C virus (HCV) RNA encoding the NS5 region (HCV-NS5) became negative following abstinence in some patients with alcoholic liver disease (ALD). In order to clarify the relationship between alcohol misuse (abuse) and the replication of HCV, serial changes of HCV-NS5 and the titer of HCV (HCV-titer) in blood after abstinence were studied in 11 male patients with ALD. Disappearance of HCV-NS5 after abstinence was found in five out of 11 patients (45%) and HCV-titer in blood decreased in all of these cases. In one patient, HCV-NS5 became positive and HCV-titers increased again following resumption of alcohol misuse. The etiology of liver disease in heavy drinkers was subdivided into three categories: alcohol alone, alcohol and HCV, and HCV alone, according to the diagnostic criteria of the Japanese research group for ALD. The etiology in four patients was a combination of alcohol and HCV, and was HCV alone in the remaining seven patients. In all four patients of the alcohol and HCV group, and one out of seven patients in the HCV alone group, HCV-NS5 became negative and HCV-titer decreased after abstinence. The decrease in HCV-titer was not related to the HCV genotypes. These results suggest that alcohol misuse may enhance the replication of HCV.

Adult↗

Facial injuries from falling: age-dependent characteristics.

A retrospective analysis was undertaken of 108 patients with facial injuries from falling who presented at the Plastic Surgery Unit of the Toyo-oka Public Hospital from 1988 to 1990. Facial injuries from falling were common in little children, in those < 6 years of age comprising 45.4% of injuries. Age-dependent characteristic injury sites were found (i.e., in those < 2 years old, the forehead; in small children, the chin; in students, the lip; and in older persons, the cheek); this disparity can be explained by the mechanism of injury. The injury pattern also depended on age, varying activities, and tissue strength. In children of < 6 years of age, small lacerations on the forehead or chin were most common, but even conservative treatment could achieve good results. On the other hand, inadequate suturing by emergency room physicians brought on poor results. In adults, abrasions and traumatic tattoos occurring with late-night inebriation tended to develop some sequelae.

Accidental Falls↗

Immunosuppressive activity of fosfomycin on human T-lymphocyte function in vitro.

Recent investigations have shown that some antibiotics also work as immunomodulators. We have recently reported that fosfomycin (FOM) has an immunomodulatory effect on human B-cell activation. FOM is a unique antibiotic which is chemically unrelated to any other known antibacterial agent. In the present study, we examined the effect of FOM on human T-cell function. FOM inhibited the proliferation of human lymphocytes induced by polyclonal T-cell mitogens in a dose-dependent manner. FOM also strongly suppressed mixed lymphocyte reaction and interleukin-2 (IL-2) production by T cells. Moreover, FOM inhibited the expressions of IL-2 receptor (CD25) and transferrin receptor (CD71) on the activated T-cell surfaces. These data suggest that FOM may block the T-cell division during the transition from G1 to S phase of the cell cycle. Combined treatment with FOM and low-dose cyclosporin A or FK506 caused additive or synergistic suppression of T-cell proliferation, but not on IL-2 receptor expression. It seems that the mode of action of FOM on T-cell function involves a specific suppression of IL-2 production.

Animals↗

Metabolic activation of aflatoxin B1 by human placental microsomes.

The metabolic activation of aflatoxin B1 by human placental microsomes was studied. Aflatoxin B1 showed relatively high mutagenic activity in Ames test when incubated with human placental microsomes. Addition of alpha-naphthoflavone or aminoglutethimide, known inhibitors of cytochrome P450 1A and P450 19, respectively, into the test system partially inhibited the mutagen-producing activity. It was suggested that the activation of aflatoxin B1 in human placental microsomes is mediated by at least these two forms of cytochrome P450.

Aflatoxin B1↗

High susceptibility to aflatoxin B1 and benzo[a]pyrene of BALB3T3 A31-1-1 cells expressing monkey CYP1A1.

The monkey CYP1A1 has been expressed in BALB 3T3 A31-1-1 cells and the expressed proteins were assayed for their capacity to activate aflatoxin B1 (AFB1) and benzo[a]pyrene (B[a]P). The transformed cells were approximately 5.4- and 4.7-fold more sensitive to AFB1 and B[a]P than the parental cells, respectively. These results indicate that monkey CYP1A1 cDNA encoded a functional protein and that the expressed CYP1A1 enzyme is active for the activation of B[a]P as well as AFB1 to produce toxic metabolites.

3T3 Cells↗

[Coagulation and fibrinolysis systems in bronchoalveolar lavage fluid in irradiated lung of rabbits].

Pulmonary fibrin deposition suggests the involvement of coagulation and fibrinolysis in pulmonary inflammation. The present study was designed to investigate the alterations of coagulation and fibrinolysis in rabbits that received thoracic irradiation. Serial bronchoalveolar lavage (BAL) was performed after the irradiation, and procoagulant activity (PCA) and tissue plasminogen activator (t-PA) were measured in BAL fluids. PCA increased from 2 to 8 weeks after irradiation with increased number of macrophages and increased PCA per macrophage. T-PA also increased with a significant difference at 4 weeks compared to controls. Although irradiation activated both PCA and t-PA, PCA increased prior to t-PA and the elevation lasted longer. It was concluded that activation of the coagulation system promotes pulmonary fibrin deposition and may contribute to the progression of pulmonary injury.

Animals↗